EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.

A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation. OBJECTIVE: This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions. METHODS: The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry. RESULTS: Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro. CONCLUSIONS: This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.

A classification of chronic rhinosinusitis with nasal polyps based on structured histopathology.

AIMS: In chronic rhinosinusitis with nasal polyps (CRSwNP), tools based on objective evidence, such as histopathology, are needed to assist clinical decision-making. The main aim of this exploratory investigation was to determine whether structured histopathology could be used to classify CRSwNP in homogeneous histological clusters. METHODS AND RESULTS: A cohort of 135 CRSwNP patients was assessed, on the basis of clinicopathological features: allergic fungal rhinosinusitis (17 patients); non-steroidal anti-inflammatory drug-exacerbated respiratory disease (19 patients); intrinsic asthma (18 patients); extrinsic asthma (21 patients); allergy (21 patients); histologically eosinophilic (22 patients); and histologically non-eosinophilic (17 patients). For structured histopathology, we considered: the degree of inflammation; eosinophil count; eosinophil aggregates; neutrophil infiltration; goblet cell hyperplasia; basement membrane thickening; fibrosis; hyperplastic/papillary changes; squamous metaplasia; mucosal ulceration; and subepithelial oedema. Cluster analysis identified four distinct sets of cases. On discriminant analysis, the global error rate was 1.48%, and the stratified error rates were 4.34%, 0%, 0%, and 0% for clusters 1, 2, 3 and 4, respectively. Cluster 1 was characterised by infrequent fibrosis (<4.5% of cases). Cluster 2 mainly featured neutrophil infiltration in 100% of cases, hyperplastic/papillary changes in 70% of cases, and fibrosis in 65% of cases. Cluster 3 showed fibrosis in 100% of cases. Cluster 4 showed hyperplastic/papillary changes in 100% of cases, and fibrosis in 92% of cases. CONCLUSIONS: This study shows that cluster analysis can identify different histotypes among CRSwNP patients. The next step will be to investigate, in a larger series, the clinical (e.g. prognostic) implications of identifying such homogeneous clusters of patients with CRSwNP on the basis of their structured histopathology.

[Morphogenesis of the stromal tissue of nasal polyps].

The objective of the present work was to study various stages of morphogenesis of the stromal tissue of nasal polyps. The materials for the investigation were harvested during endoscopic polypotomies in the nose. They were used to obtain the preparations that were stained by the histological and histochemical methods. The immunochemical studies were carried out using monoclonal antibodies against differentiation clusters, such as CD20, CD31, and vascular endothelial growth factor (VEGF). The study has demonstrated that the growth and evolution of the nasal polyps are accompanied by sequential alterations in the morphological structure of their stromal tissue. The results of the investigations were used to develop the original classification of the selected stages of morphogenesis of the stromal tissue of nasal polyps. The following stages were distinguished: edematous one, inflammatory cellular infiltration, fibrous cirrhotic alterations, and vasculogenesis or neoangiogenesis.

Efficacy of systemic steroid treatment in sinonasal polyposis.

AIM: Nasal polyposis is an inflammatory disease of unknown origin. Systemic steroid treatment is effective not only in decreasing polyp size but also in controlling mucosal inflammation. We evaluated the efficacy of mean-term systemic corticosteroid treatment in nasal polyposis clinically and radiologically. METHODS: Seventy-five patients with nasal polyposis were included in this study. Patients were treated with methylprednisolone for 20 days. Clinical response was evaluated by nasal symptom scores and changes in polyp size; disease extent was assessed by paranasal sinus tomography. Nasal symptom score, polyp size, and disease extent were reevaluated after therapy. RESULTS: Twenty-one (28%) of 75 patients were female, and 54 (72%) were male. The mean age was 41.63 ± 11.04 with a range of 17 to 80 years. As shown radiologically, 26.7% (n = 20) of patients completely healed, and 41.3% (n = 31) partially healed, whereas there was no improvement in 32% (n = 24). There was a statistically significant improvement in radiological assessment (P < 0.01). The sense of smell showed the greatest improvement (56.98%). The least-improved symptoms were facial pain and headache (37.74%). There was a statistically significant decrease in polyp grade (P < 0.01). CONCLUSIONS: Systemic steroid treatment caused a decrease in all nasal symptoms and polyp size and improved paranasal computed tomography results. In addition, it shortened the duration of surgery and improved the quality of the procedure. Systemic steroid treatment also contributed to the prevention of recurrence.

Chronic rhinosinusitis: epidemiology and medical management.

Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author's personal experience.

Contemporary Classification of Chronic Rhinosinusitis Beyond Polyps vs No Polyps: A Review.

Importance: Chronic rhinosinusitis (CRS) is a broadly defined process that has previously been used to describe many different sinonasal pathologic conditions from odontogenic sinusitis and allergic fungal sinusitis to the more contemporary definition of broad inflammatory airway conditions. Previous classification systems have dichotomized these conditions into CRS with nasal polyps and CRS without nasal polyps. However, clinicians are learning more about the inflammatory subtypes of CRS, which can lead to improved delivery and effectiveness of treatment. Observations: In clinical practice, treatment decisions are often based on observable findings, clinical history, presumed disease, and molecular pathophysiologic characteristics. A proposed classification system is simple and practical. It proposes that the functional anatomical compartments involved create the first level of separation into local and diffuse CRS, which are usually unilateral or bilateral in distribution. Diffuse does not imply "pansinusitis" but simply that the disease is not confined to a known functional anatomical unit. This classification takes into account whether local anatomical factors are associated with pathogenesis. Then the inflammatory endotype dominance is separated into a type 2 skewed inflammation, as this has both causal and treatment implications. The non-type 2 CRS encompasses everything else that is not yet known about inflammation and may change over time. The phenotypes or clinical examples are CRS entities that have been described and how they align with this system. Conclusions and Relevance: Although research continues to further define the subtypes of CRS into phenotypes and endotypes, the proposed classification system of primary CRS by anatomical distribution and endotype dominance allows for a pathway forward.

[Classification of chronic rhinosinusitis with nasal polyps based on eosinophilic inflammation].

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disorder characterized by chronic sinonasal mucosal inflammation. CRSwNP can be subdivided into two types based on eosinophilic inflammation: eosinophilic CRSwNP (Eos CRSwNP) and non-eosinophilic CRSwNP (Non-Eos CRSwNP). Eos CRSwNP and Non-Eos CRSwNP demonstrate distinct clinical manifestations, treatment outcomes, and cellular and immunopathologic characteristics. However, currently, there is no unified and generally accepted standard to define the Eos CRSwNP. The aim of this review is to compare the advantages and disadvantages of current methods used to classify Eos CRSwNP, in order to lay foundation for further study.

Histological aspects of rhinosinusal polyps.

UNLABELLED: Contemporary cohort cross-sectional study. INTRODUCTION: Despite its importance for an accurate diagnosis, histology differences among nasal polyps and its clinical implications are rarely reported in the literature. The existing papers classify polyp samples without concern for prior treatments, which could influence the results attained. AIMS: carry out a morphological study, through light microscopy, of nasal polyps' structural alterations in the absence of any type of prior treatment and histologically classify it in relation to studies published in the literature. MATERIALS AND METHODS: We studied 89 patients with nasosinusal polyps without prior treatment. Polyp samples were collected by outpatient biopsy and analyzed through light microscopy after dyeing with hematoxylin-eosin. RESULTS: Samples were classified in the following way: Edematous or eosinophilic polyp 65 cases (73%); fibro-inflammatory polyp: 16 cases (18%); Polyp with Sero-mucinose gland hyperplasia: 06 cases (6.7%) and polyp with stroma atypia: 2 cases (2.3%). DISCUSSION: eosinophilic pattern prevailed in the patients with nasosinusal polyps of the population studied. This pattern is similar to the ones found in the major studies, which, however, do not mention prior treatment. CONCLUSION: after analyzing the polyps' histological characteristics, we noticed that the untreated polyps present a predominantly eosinophilic pattern.

Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype.

BACKGROUND: Revision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes. METHODS: Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes. RESULTS: ESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin-exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. At median follow-up of 28 months (interquartile range [IQR], 10-47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and "all other CRS" 4% at median follow-up duration of 36, 28, 41, 37, 44, and 26 months, respectively. CONCLUSION: All CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT-22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes.

Local immunoglobulin production in nasal polyposis is modulated by superantigens.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (NP) represents a persistent inflammation often characterized by local hyper-immunoglobulinaemia and the presence of specific IgE to Staphylococcus aureus enterotoxins (SAEs). We aimed to study the systemic and local production of Igs in relation to plasma cells, B cells and specific IgE to SAEs. METHODS: Concentrations of IgE, IgG, IgM, IgA, IgG subclasses and specific IgE to SAE were determined on tissue homogenates and serum from 15 CRS patients with NP, 15 CRS without NP and 10 control patients. Tissue cryo-sections were stained for CD19, CD20 and CD138 to demonstrate B and plasma cells. RESULTS: IgA, IgG and IgE concentrations were significantly higher in tissue homogenates, but not in serum, of NP compared with CRS and control subjects. NP with specific IgE to SAEs had significantly higher concentrations of IgG and IgE, and also showed a significantly higher fraction of IgG4 (P=0.003) and a lower fraction of IgG2 (P=0.04) than those without specific IgE production. Furthermore, naïve CD19(+) B cell and plasma cell counts (CD138(+)) were significantly higher in NP tissue compared with controls or CRS. CONCLUSIONS: The difference in IgE, IgG and IgA expression between NP tissue and serum, supported by increased numbers of plasma cells, suggests a local production of these Igs in NP in response to a chronic microbial trigger. The local immune response to SAE is associated with a further increased production of IgE and IgG, and a shift in IgG subclasses.

The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict?

OBJECTIVES: The Lund-Mackay score is widely used in assessment of chronic rhinosinusitis. We aimed to describe its relationship to other measures of pre- and post-treatment health status. STUDY DESIGN: Multicenter prospective study of 1840 patients undergoing surgery for chronic rhinosinusitis in the UK. RESULTS: There was no absolute threshold for surgery, but patients with higher Lund-Mackay scores underwent more extensive surgery. There was no correlation between Lund-Mackay and SNOT-22 scores. The Lund-Mackay increased with increasing grade of polyposis. The Lund-Mackay score was associated with symptom reduction (coefficient = 0.24, P = 0.02) complication rates (odds ratio, 1.08, 95%CI 1.06 to 1.1), and revision rates (odds ratio, 1.03, 95% CI 1.001 to 1.06). CONCLUSIONS: The Lund-Mackay score measures a different aspect of disease to "subjective" symptom scores. However, it correlates well with other markers of disease severity, the nature of surgery offered, and its outcome. SIGNIFICANCE: This demonstrates the strengths and limitations of a commonly used staging system.

Refinement of the nasalisation technique for nasal polyposis.

BACKGROUND: Radical ethmoidectomy for nasal polyposis (nasalisation) tends to offer better results than functional ethmoidectomy in terms of recurrence. We have been performing the nasalisation technique since 2004, but late complications such as mucoceles were noted in several patients. We implemented some modifications to the nasalisation technique in order to reduce the complication rate while obtaining a similar recurrence rate. METHODOLOGY AND PRINCIPAL: Retrospective study on the files of patients operated for diffuse nasal polyposis after 24months of follow-up. Group A included 45 patients (90 sides) operated with the classical nasalisation technique, and group B included 74 patients (148 sides) operated with the modified technique. RESULTS: Preoperative endoscopic grading results did not show any significant difference between groups. Recurrence rates at 24months of postoperative follow-up were of 22.2% and of 18.9% for group A and B respectively. This difference was not statistically significant. Complication rates were of 37.8% and 8.8% for Group A and Group B respectively. Complication rate was significantly lower for group B (P=0.002, standard deviation of 0.467). CONCLUSIONS: The modified nasalisation technique offers the same functional results than the classical technique, but with a significant reduction of the late complication rate.

Pathophysiological classification of chronic rhinosinusitis.

BACKGROUND: Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD: Statistical patterns of subjective and objective findings were assessed by retrospective chart review. RESULTS: CRS patients were readily divided into those with (50/99) and without (49/99) polyposis. Aspirin sensitivity was limited to 17/50 polyp subjects. They had peripheral blood eosinophilia and small airways obstruction. Allergy skin tests were positive in 71% of the remaining polyp subjects. IgE was<10 IU/ml in 8/38 polyp and 20/45 nonpolyp subjects (p = 0.015, Fisher's Exact test). CT scans of the CRS without polyp group showed sinus mucosal thickening (probable glandular hypertrophy) in 28/49, and nasal osteomeatal disease in 21/49. Immunoglobulin isotype deficiencies were more prevalent in nonpolyp than polyp subjects (p < 0.05). CONCLUSION: CRS subjects were retrospectively classified in to 4 categories using the algorithm of (1) polyp vs. nonpolyp disease, (2) aspirin sensitivity in polyposis, and (3) sinus mucosal thickening vs. nasal osteomeatal disease (CT scan extent of disease) for nonpolypoid subjects. We propose that the pathogenic mechanisms responsible for polyposis, aspirin sensitivity, humoral immunodeficiency, glandular hypertrophy, eosinophilia and atopy are primary mechanisms underlying these CRS phenotypes. The influence of microbial disease and other factors remain to be examined in this framework. We predict that future clinical studies and treatment decisions will be more logical when these interactive disease mechanisms are used to stratify CRS patients.

[Rational treatment of nasal polyposis]. / Trattamento ragionato della poliposi nasale.

Despite the therapeutical advances of the last decade, nasal polyposis represents still a problem for rhinology, practitioners. A number of hypotheses have been formulated about its etiopathogenesis, but no one is confirmed, so that nowadays therapy continues to be only symptomatic and does not cure definitively the underlying pathology. Recurrences are frequent and discourage both the practitioner and the patient. Purpose of this paper is to illustrate Authors' therapeutical rationale aimed to reestablish nasal flow, reduce rhinorrhea, improve olfaction, decrease rhinosinusinusal infection rate and maintain as long as possible such a symptomatic improvement. These targets are best achieved by a combination of medical and surgical treatments in order to optimize the results and reduce the side-effects of both the therapeutical options. Moreover the treatment should be tailored on each patient and follow up should be careful and performed at regular interval. Authors reviewed the clinical records of patients who underwent surgery for nasal polyposis between 2002 and 2004 at Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy, with a minimum follow-up of 12 months. All patients underwent the complete set of diagnostic work-up. The choice between surgical or medical options was based on both the kind of the polyposis and the staging of the pathology. The therapy was as more "personalized" as possible, but a homogeneity of treatment was maintained. The results show that a correct "staging" of the patient allows an appropriate therapy and reduces recurrence rate. In conclusion, authors report their experience and propose a scheme of diagnostic work-up in order to define grading/staging of the pathology and establish a "tailored" therapeutic protocol aimed to control a pathology which is rarely definitively treated.

Histopathological classification of refractory chronic rhinosinusitis with nasal polyps.

OBJECTIVE: To delineate the histopathological characteristics of nasal mucosa in refractory chronic rhinosinusitis with nasal polyps (CRSwNP) in order to demonstrate subtypes of nasal polyps and their potential relation with lower airway comorbidity. STUDY DESIGN: Clinical- and pathological-based cross-sectional study Methods: Nasal polyp specimens were prospectively collected from patients with refractory CRSwNP referred to our institution for endoscopic sinus surgery. Oral and topical steroids were stopped 1 month before surgery. The pathological analysis was conducted by 2 independent reviewers with light microscopy on Hematoxylin-Eosin-Saffron stained slides. Each observer fulfilled a standardized protocol with cell count and stromal characterization on the most representative field. Mean grading scores were established. Morphological aspects were compared with the cell distribution and the clinical conditions. RESULTS: Among 36 patients, three subtypes of nasal polyps were depicted: eosinophilic edematous (64%), fibrous (9%) and intermediate with mixed edematous and collagen stromal structure (27%). Basement membrane thickening and seromucous gland hyperplasia were observed in the fibrosis sub-type (p<0.03). Eosinophilic mucosal infiltrate was significantly increased (p=0.026) in patients with concomitant pulmonary disease (n=21). Nasal polyp distribution was not influenced by asthma, allergy, previous surgery and smoking. CONCLUSION: Our 3-subtype classification of refractory CRSwNP in Caucasian population shows a predominant edematous structure whatever the clinical conditions may have been. Eosinophilia as a major factor of adaptive immune response in nasal inflammation is a feature of concomitant pulmonary disease. Further studies concerning mucosal remodelling and outcome assessment after sinus surgery are required to evaluate the impact of our classification on a daily basis.

Differential expression of periostin in the nasal polyp may represent distinct histological features of chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is thought to be a multifactorial disease, and it is classified into a number of subtypes according to clinicohistological features. Periostin, a 90-kDa secreted protein, was reported to exist in nasal polyps (NPs) associated with CRS. We compared the expression of periostin with the degree of eosinophilic infiltration as well as tissue remodeling. MATERIALS AND METHODS: Tissue samples were collected from 28 patients of CRS with NPs, and clinicohistological features were evaluated. The pattern of periostin expression was assessed immunohistochemically. RESULT: Two patterns of periostin expression was observed in nasal polyps: "diffuse type", in which periostin was expressed throughout the lamina propria starting just below the basement membrane, and "superficial type", in which the protein was detected only in the subepithelial layers between the basement membrane and the nasal gland. The average infiltrated eosinophil count in the diffuse type was significantly higher than that in the superficial type (diffuse type 360.5±393.0 vs. superficial type 8.46±13.81, p=0.001). Tissue remodeling was observed in 17 (85.0%) of the 20 diffuse-type nasal polyps, but only in one (12.5%) of the eight superficial-type nasal polyps (p<0.001). CONCLUSION: At least two distinct patterns of periostin expression were observed in the nasal polyps associated with CRS in accordance with the heterogeneous mechanisms underlying the pathogenesis of CRS with NPs.

Topical corticosteroids in nasal polyposis.

Nasal polyps are the common end-point of a number of conditions characterised by inflammation and are rarely 'curable' in its true sense. After consideration of the underlying aetiology and confirmation of the diagnosis, they are normally managed by a combination of medical and surgical interventions. Of these, topical corticosteroids have proved to be the medical treatment of choice. The objectives of the medical management are to eliminate or reduce the size of polyps, re-establish nasal airway and nasal breathing, improve or restore the sense of smell, and prevent recurrence of nasal polyps. The mechanism of action of corticosteroids may be by a multifactorial effect on various aspects of the inflammatory reaction, the effect being initiated by their binding to a specific cytoplasmic glucocorticoid receptor. At a cellular level, there is a reduction in the number of antigen-presenting cells, in the number and activation of T cells, in the number of mast cells, and in the number and activation of eosinophils. When polyps are large (grade 3) topical medication is difficult to instil in a very blocked nose and surgery or short term systemic corticosteroids may be required. Topical corticosteroids are of use in the primary treatment of nasal polyps when they are of a small or medium size (grades 1 and 2) and in the maintenance of any therapeutic improvement. The efficacy of topical corticosteroids such as betamethasone sodium phosphate nose drops, beclomethasone dipropionate, fluticasone propionate and budesonide nasal sprays in reducing polyp size and rhinitis symptoms has been demonstrated in several randomised, placebo-controlled trials. Beclomethasone dipropionate, flunisolide and budesonide sprays have also been shown to delay the recurrence of polyps after surgery. Placebo-controlled studies of agents that have shown a significant clinical effect in the management of nasal polyposis are reviewed.

Inverted papilloma: an analysis of 87 cases.

A group of 87 patients with inverted papilloma, a locally aggressive benign sinonasal tumor, were treated over the past 15 years. Selection of therapy depends on an accurate radiographic assessment of the extent of tumor. The tumor's local aggressiveness, high rate of recurrence, associated malignancy, and multicentric tendency have led most workers to advocate radical surgical removal of the tumor by lateral rhinotomy and en bloc resection of the ethmoid labyrinth. Radiographic evaluation by computed tomography scanning and magnetic resonance imaging permits identification of a small group of patients who have limited lesions and may be candidates for conservative tumor resection by intranasal or transantral sphenoethmoidectomy. Among our ten patients treated with conservative surgery, there was recurrence in one case (10%). Seventy-five patients underwent rhinotomy and medial maxillectomy, with seven cases recurring (9%). The overall recurrence rate was 9% (8 of 87). Among the 87 cases, 5 patients had carcinoma (6%). The literature is reviewed and the principles of case selection and management are discussed.